Loss of epigenetic information as a cause of mammalian aging.
DNA damage
RCM
aging
chromatin
epigenetic clock
epigenetic reprogramming
relocalization of chromatin modifier
senescence
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
19 01 2023
19 01 2023
Historique:
received:
14
09
2021
revised:
09
08
2022
accepted:
15
12
2022
pmc-release:
19
01
2024
pubmed:
14
1
2023
medline:
25
1
2023
entrez:
13
1
2023
Statut:
ppublish
Résumé
All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.
Identifiants
pubmed: 36638792
pii: S0092-8674(22)01570-7
doi: 10.1016/j.cell.2022.12.027
pmc: PMC10166133
mid: NIHMS1859595
pii:
doi:
Substances chimiques
Nucleoproteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
305-326.e27Subventions
Organisme : NEI NIH HHS
ID : R01 EY019703
Pays : United States
Organisme : NIA NIH HHS
ID : F99 AG073499
Pays : United States
Organisme : NIA NIH HHS
ID : K99 AG068303
Pays : United States
Organisme : NIA NIH HHS
ID : K99 AG055683
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG028730
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG051449
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY003790
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG019719
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK056799
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG065403
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK097598
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG064223
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG028730
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG016694
Pays : United States
Organisme : NIA NIH HHS
ID : R00 AG055683
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007118
Pays : United States
Organisme : NIA NIH HHS
ID : K99 AG070102
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG023480
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests D.A.S. is a consultant, inventor, board member, and in some cases an investor in Life Biosciences (developing reprogramming medicines), InsideTracker, Zymo, EdenRoc Sciences/Cantata/Dovetail/Metrobiotech, Caudalie, Galilei, Immetas, Animal Biosciences, Tally Health, and more. See https://sinclair.hms.harvard.edu/david-sinclairs-affiliations. E.M.M., M. Blanchette, and M. Bhakta are employees of Catata Bio/Dovetail. Y.C.C., W.G., and X.Y. are employees of Zymo Research. A.J.W. advises Kate Therapeutics and Frequency Therapeutics and is a co-founder, adviser, and equity holder of Elevian, which sponsors Wagers Lab research. L.S. was an employee of Vium. Y.R.L. and L.A.R. are equity owners of Life Biosciences. M.S.B. and D.L.V. advise EdenRoc Sciences. A patent application was filed on the reprogramming methods.
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